Single-nucleus RNA sequencing reveals that macrophages and smooth muscle cells promote carotid atherosclerosis progression through mitochondrial autophagy

Abstract

Abstract Objects Carotid atherosclerotic plaques are the manifestation of atherosclerosis in the carotid arteries and can significantly increase the incidence of cerebrovascular disease. Macrophages and smooth muscle cells are crucial for their development. Our research aimed to reveal the mechanism of carotid atherosclerotic plaque formation. Methods The collected carotid plaques were processed to extract RNA and create a DNA library. After completing these steps, Single-nucleus RNA Sequencing analysis was performed using R language to analyze cell subpopulations. KEGG pathway, cellular communication, and the proposed time-series analysis were performed for differential genes. Results we performed single-cell nuclear sequencing of the carotid plaque tissue and identified 11 cell types, and the macrophages were divided into five different macrophage subpopulations. The macrophages and smooth muscle cells in the patients with symptomatic carotid atherosclerotic plaques caused intraplaque cell death via the mitochondrial autophagic pathway, resulting in plaque instability and rupture, which in turn led to clinical cardiovascular and cerebrovascular events. Conclusions The findings provide new insights into carotid atherosclerosis formation, and this may provide new directions for the prevention and treatment of carotid atherosclerosis.